Mapping Sex-Based Multimorbidity Networks in Type 1 Diabetes: A Real-World Study from Shanghai

Yuxuan Sheng¹Ping He²Junlei Su¹Zhongyun Zhang¹Tingyu Zhang¹Haolei Pan¹Huayan Yao¹Yanbin Xue¹Xueyuan Li³Bin Cui¹Zizheng Zhang^1*Weiqiong Gu^1*

• ¹Shanghai Institute of Endocrine and Metabolic Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
• ²Shanghai Hospital Development Center, Shanghai, China
• ³Wonders Information Co Ltd, Shanghai, China

Background: Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disorder associated with a substantial metabolic burden. However, large-scale, real-world studies assessing sex-specific multimorbidity patterns in T1DM remain limited. Objective: To characterize the clinical profiles and multimorbidity patterns in patients with T1DM, using age-and sex-matched individuals with type 2 diabetes mellitus (T2DM) as controls. Methods: Using the Shanghai Hospital Link Database, we identified patients aged 10–79 years with a first T1DM-coded diagnosis between 2014 and 2023 and selected 1:1 sex-and index-age–matched T2DM controls. Clinical characteristics were compared between groups overall and stratified by sex. Sex-stratified multimorbidity networks were constructed and analyzed using standard network metrics. Subgroup-unique comorbid disease pairs were identified using the Salton Cosine Index. Results: We included 18,971 patients with T1DM and 18,971 matched T2DM controls. Compared with T2DM, T1DM showed shorter observed follow-up, higher glycated hemoglobin, higher high-This is a provisional file, not the final typeset article density lipoprotein cholesterol, and lower triglyceride, with more pronounced differences among females. Hypertension and dyslipidemia were the most central comorbidities across all networks, closely linked to cardiovascular and cerebrovascular conditions. The female T1DM network exhibited greater complexity and connectivity than the male T1DM network. Subgroup-unique pairs were more frequent in T1DM, including peripheral vascular disease–nonalcoholic fatty liver disease and diabetic eye complications–stroke in males, and neuropathy–osteoporosis, nephropathy–chronic gastritis, and chronic gastritis–asthma in females. Conclusion: We identified shared cardiometabolic comorbidities (hypertension and dyslipidemia) across diabetes types and sexes, and sex-specific multimorbidity co-occurrence signatures in T1DM. These findings support integrating blood pressure and lipid optimization with glycemic management, and underscore the need for sex-sensitive surveillance of subgroup-specific clusters, highlighting broader multisystem clustering in females and vascular-risk co-occurrence signals in males that may warrant intensified multifactorial atherosclerotic cardiovascular disease prevention.